The overall aim of our proposed study is to examine the effects of marijuana on the development of frontal lobe systems and their function in marijuana-smoking adolescents and healthy non-using adolescents by applying a complementary set of magnetic resonance (MR) techniques and neuropsychological assessments. Our previous investigations have identified age-related differences in cognition, morphometry and functional magnetic resonance imaging (fMRI) in healthy adolescents. Furthermore, we have found an association between early onset of marijuana use and poorer neuropsychological performance, as well as abnormal cortical activation in the anterior cingulate and dorsal lateral prefrontal cortex on measures of motor and memory function shortly after cessation of marijuana use in adults. We therefore propose to examine the effects of age of onset of marijuana use in two adolescent cohorts: 1) a 14 year old cohort who report a minimum of 100 episodes of using marijuana; and 2) an 18 year old cohort who report the same amount of marijuana usage, but who did not begin smoking until after their 16th birthday. Both groups will be compared to age matched non-smoking adolescents. Although significant evidence has accumulated indicating an association between marijuana use and altered frontal-executive function, it has been difficult to study and document functional human brain changes associated with marijuana, particularly during adolescence. In this proposal, we will take advantage of the high spatial resolution and increased signal to noise offered by complementary high field MR techniques to investigate chemical and functional effects of marijuana use in frontal brain regions that are known to undergo maturational refinements during adolescence. Specifically, this study will incorporate focal functional MR BOLD techniques using cognitive and affective challenge paradigms at 3 Tesla, and single voxel GABA spectroscopy of the cingulate at 4 Tesla, with neuropsychological measures of executive function, in order to address the question of whether developing frontal brain regions are more vulnerable to illicit drug use when there is an early versus late onset of marijuana use. We believe these complimentary measures of brain function will provide new insights into the neural mechanisms of inhibitory processing and decision- making in adolescents who abuse marijuana, which has implications for early intervention and remediation. [unreadable] [unreadable] [unreadable]